In developing countries of the tropics and subtropics, rheumatic heart disease is currently the most common form of cardiac damage. The streptococcal M protein is the major virulence factor of this bacterium by virtue of its ability to impart resistance to phagocytic attack. In order to approach the question of a vaccine to prevent streptococcal disease, it is important to understand the M molecule in more molecular detail. The major questions we propose to answer are: 1.) are there common sequences or common structural determinants in all (or most) M proteins? and 2.) in the region of the M molecule required for function, what specific changes render the molecule inactive. For this study, we have chosen to start with the M6 molecule because it is one of the three that is best understood and because it is available purified in "native" form (48). We propose to clone the structural gene for M6 into Escherichia coli to facilitate the molecular dissection of this molecule which should lead to an understanding of its relation to other M proteins and to an understanding of the relation of M protein structure to its function.